Newly Diagnosed Infection After Admission for Acute Heart Failure: From the KCHF Registry

[Background] No studies have explored the association between newly diagnosed infections after admission and clinical outcomes in patients with acute heart failure. We aimed to explore the factors associated with newly diagnosed infection after admission for acute heart failure, and its association with in‐hospital and post‐discharge clinical outcomes. [Methods and Results] Among 4056 patients enrolled in the Kyoto Congestive Heart Failure registry, 2399 patients without any obvious infectious disease upon admission were analyzed. The major in‐hospital and post‐discharge outcome measures were all‐cause deaths. There were 215 patients (9.0%) with newly diagnosed infections during hospitalization, and 2184 patients (91.0%) without infection during hospitalization. The factors independently associated with a newly diagnosed infection were age ≥80 years, acute coronary syndrome, non‐ambulatory status, hyponatremia, anemia, intubation, and patients who were not on loop diuretics as outpatients. The newly diagnosed infection group was associated with a higher incidence of in‐hospital mortality (16.3% and 3.2%, P<0.001) and excess adjusted risk of in‐hospital mortality (odds ratio, 6.07 [95% CI, 3.61–10.19], P<0.001) compared with the non‐infection group. The newly diagnosed infection group was also associated with a higher 1‐year incidence of post‐discharge mortality (19.3% in the newly diagnosed infection group and 13.6% in the non‐infection group, P<0.001) and excess adjusted risk of post‐discharge mortality (hazard ratio, 1.49 [95% CI, 1.08–2.07], P=0.02) compared with the non‐infection group. [Conclusions] Elderly patients with multiple comorbidities were associated with the development of newly diagnosed infections after admission for acute heart failure. Newly diagnosed infections after admission were associated with higher in‐hospital and post‐discharge mortality in patients with acute heart failure

Appetite loss at discharge from acute decompensated heart failure: Observation from KCHF registry

OBJECTIVE: The complex link between nutritional status, protein and lipid synthesis, and immunity plays an important prognostic role in patients with heart failure. However, the association between appetite loss at discharge and long-term outcome remains unclear. METHODS: The Kyoto Congestive Heart Failure registry is a prospective cohort study that enrolled consecutive patients hospitalized for acute decompensated heart failure (ADHF) in Japan. We assessed 3528 patients alive at discharge, and for whom appetite and follow-up data were available. We compared one-year clinical outcomes in patients with and without appetite loss at discharge. RESULTS: In the multivariable logistic regression analysis using 19 clinical and laboratory factors with P value 1.0mg/dL (OR: 1.49, 95%CI: 1.04-2.14, P = 0.03), and presence of edema at discharge (OR: 4.30, 95%CI: 2.99-6.22, P<0.001) were associated with an increased risk of appetite loss at discharge, whereas ambulatory status (OR: 0.57, 95%CI: 0.39-0.83, P = 0.004) and the use of ACE-I/ARB (OR: 0.70, 95% CI: 0.50-0.98, P = 0.04) were related to a decreased risk in the presence of appetite loss. The cumulative 1-year incidence of all-cause death (primary outcome measure) was significantly higher in patients with appetite loss than in those without appetite loss (31.0% vs. 15.0%, P<0.001). The excess adjusted risk of appetite loss relative to no appetite loss remained significant for all-cause death (hazard ratio (HR): 1.63, 95%CI: 1.29-2.07, P<0.001). CONCLUSIONS: Loss of appetite at discharge was associated with worse 1-year mortality in patients with ADHF. Appetite is a simple, reliable, and useful subjective marker for risk stratification of patients with ADHF

Association of an increase in serum albumin levels with positive 1-year outcomes in acute decompensated heart failure: A cohort study

Background: Despite the prognostic importance of hypoalbuminemia, the prognostic implication of a change in albumin levels has not been fully investigated during hospitalization in patients with acute decompensated heart failure (ADHF). Methods: Using the data from the Kyoto Congestive Heart Failure registry on 3160 patients who were discharged alive for acute heart failure hospitalization and in whom the change in albumin levels was calculated at discharge, we evaluated the association with an increase in serum albumin levels from admission to discharge and clinical outcomes by a multivariable Cox hazard model. The primary outcome measure was a composite of all-cause death or hospitalization for heart failure. Findings: Patients with increased albumin levels (N = 1083, 34.3%) were younger and less often had smaller body mass index and renal dysfunction than those with no increase in albumin levels (N = 2077, 65.7%). Median follow-up was 475 days with a 96% 1-year follow-up rate. Relative to the group with no increase in albumin levels, the lower risk of the increased albumin group remained significant for the primary outcome measure (hazard ratio: 0.78, 95% confidence interval: 0.69–0.90: P = 0.0004) after adjusting for confounders including baseline albumin levels. When stratified by the quartiles of baseline albumin levels, the favorable effect of increased albumin was more pronounced in the lower quartiles of albumin levels, but without a significant interaction effect (interaction P = 0.49). Conclusions: Independent of baseline albumin levels, an increase in albumin during index hospitalization was associated with a lower 1-year risk for a composite of all-cause death and hospitalization in patients with acute heart failure

Polyphosphate Synthetic Activity of Polyphosphate:AMP Phosphotransferase in Acinetobacter johnsonii 210A

Polyphosphate:AMP phosphotransferase (PAP) has been identified as an enzyme that catalyzes the phosphorylation of AMP with inorganic polyphosphates [poly(P)] as phosphate donors. We found that the purified PAP of Acinetobacter johnsonii 210A has poly(P) synthetic activity. The PAP catalyzes the dephosphorylation of ADP and processively synthesizes poly(P) of 200 to 700 residues. Comparatively lower concentrations of MgCl(2) (20 mM) were required to obtain optimum poly(P) synthetic activity, whereas higher concentrations of MgCl(2) (100 mM) were necessary for optimum PAP activity. ADP is preferred over GDP as a phosphate donor for poly(P) synthesis. The K(m) and V(max) values for ADP in the poly(P) synthetic activity of PAP were 8.3 mM and 55 μmol min(−1) mg(−1), respectively. We concluded that the PAP of A. johnsonii 210A is a novel type of poly(P) kinase that uses ADP and GDP as substrates

Improved Secretory Production of Recombinant Proteins by Random Mutagenesis of hlyB, an Alpha-Hemolysin Transporter from Escherichia coli

Fusion proteins with an alpha-hemolysin (HlyA) C-terminal signal sequence are known to be secreted by the HlyB-HlyD-TolC translocator in Escherichia coli. We aimed to establish an efficient Hly secretory expression system by random mutagenesis of hlyB and hlyD. The fusion protein of subtilisin E and the HlyA signal sequence (HlyA(218)) was used as a marker protein for evaluating secretion efficiency. Through screening of more than 1.5 × 10(4) E. coli JM109 transformants, whose hlyB and hlyD genes had been mutagenized by error-prone PCR, we succeeded in isolating two mutants that had 27- and 15-fold-higher levels of subtilisin E secretion activity than the wild type did at 23°C. These mutants also exhibited increased activity levels for secretion of a single-chain antibody-HlyA(218) fusion protein at 23 and 30°C but unexpectedly not at 37°C, suggesting that this improvement seems to be dependent on low temperature. One mutant (AE104) was found to have seven point mutations in both HlyB and HlyD, and an L448F substitution in HlyB was responsible for the improved secretion activity. Another mutant (AE129) underwent a single amino acid substitution (G654S) in HlyB. Secretion of c-Myc-HlyA(218) was detected only in the L448F mutant (AE104F) at 23°C, whereas no secretion was observed in the wild type at any temperature. Furthermore, for the PTEN-HlyA(218) fusion protein, AE104F showed a 10-fold-higher level of secretion activity than the wild type did at 37°C. This result indicates that the improved secretion activity of AE104F is not always dependent on low temperature

Morphogenetic Study on the Maturation of Osteoblastic Cell as Induced by Inorganic Polyphosphate

Since inorganic polyphosphates [poly(P)] have an activity to induce bone differenciation in vitro and in vivo, we examined an effect of poly(P) on organelle by light microscopy and electron microscopy in Murine MC3T3-E1 osteoblastic cells. The MC3T3-E1 cells were ultrastructurally observed to possess morphological characteristics of osteoblasts. Cells cultured with poly(P) were strongly stained with an anti-collagen type I antibody but not in those cultured without poly(P). Ultrastructural analysis of cells cultured with poly(P) revealed a well-developed Golgi apparatus, swollen and elongated rough endoplasmic reticulum, large mitochondria and many coated pits. Since MC3T3-E1 cells can be transformed from a resting phase to an active blastic cell phase after supplementation with poly(P), it implies that poly(P) can be an effective material for bone regeneration

Genes from Pseudomonas sp. Strain BS Involved in the Conversion of l-2-Amino-Δ(2)-Thiazolin-4-Carbonic Acid to l-Cysteine

dl-2-amino-Δ(2)-thiazolin-4-carbonic acid (dl-ATC) is a substrate for cysteine synthesis in some bacteria, and this bioconversion has been utilized for cysteine production in industry. We cloned a DNA fragment containing the genes involved in the conversion of l-ATC to l-cysteine from Pseudomonas sp. strain BS. The introduction of this DNA fragment into Escherichia coli cells enabled them to convert l-ATC to cysteine via N-carbamyl-l-cysteine (l-NCC) as an intermediate. The smallest recombinant plasmid, designated pTK10, contained a 2.6-kb insert DNA fragment that has l-cysteine synthetic activity. The nucleotide sequence of the insert DNA revealed that two open reading frames (ORFs) encoding proteins with molecular masses of 19.5 and 44.7 kDa were involved in the l-cysteine synthesis from dl-ATC. These ORFs were designated atcB and atcC, respectively, and their gene products were identified by overproduction of proteins encoded in each ORF and by the maxicell method. The functions of these gene products were examined using extracts of E. coli cells carrying deletion derivatives of pTK10. The results indicate that atcB and atcC are involved in the conversion of l-ATC to l-NCC and the conversion of l-NCC to cysteine, respectively. atcB was first identified as a gene encoding an enzyme that catalyzes thiazolin ring opening. AtcC is highly homologous with l-N-carbamoylases. Since both enzymes can only catalyze the l-specific conversion from l-ATC to l-NCC or l-NCC to l-cysteine, it is thought that atcB and atcC encode l-ATC hydrolase and N-carbamyl-l-cysteine amidohydrolase, respectively

Activation of the FGF signaling pathway and subsequent induction of mesenchymal stem cell differentiation by inorganic polyphosphate

<p>Inorganic polyphosphate [poly(P)] is a biopolymer existing in almost all cells and tissues, although its biological functions in higher eukaryotes have not been completely elucidated. We previously demonstrated that poly(P) enhances the function of fibroblast growth factors (FGFs) by stabilizing them and strengthening the affinity between FGFs and their cell surface receptors. Since FGFs play crucial roles in bone regeneration, we further investigated the effect of poly(P) on the cell differentiation of human stem cells via FGF signaling systems. Human dental pulp cells (HDPCs) isolated from human dental pulp show the characteristics of multipotent mesenchymal stem cells (MSCs). HDPCs secreted FGFs and the proliferation of HDPCs was shown to be enhanced by treatment with poly(P). Cell surface receptor-bound FGF-2 was stably maintained for more than 40 hours in the presence of poly(P). The phosphorylation of ERK1/2 was also enhanced by poly(P). The effect of poly(P) on the osteogenic differentiation of HDPCs and human MSCs (hMSCs) were also investigated. After 5 days of treatment with poly(P), type-I collagen expression of both cell types was enhanced. The C-terminal peptide of type-I collagen was also released at higher levels in poly(P)-treated HDPCs. Microarray analysis showed that expression of matrix metalloproteinase-1 (MMP1), osteopontin (OPN), osteocalcin (OC) and osteoprotegerin was induced in both cell types by poly(P). Furthermore, induced expression of MMP1, OPN and OC genes in both cells was confirmed by real-time PCR. Calcification of both cell types was clearly observed by alizarin red staining following treatment with poly(P). The results suggest that the activation of the FGF signaling pathway by poly(P) induces both proliferation and mineralization of stem cells.</p